Lp Concentrations Research Articles

Pharmacokinetics, Pharmacodynamics, and Tolerability of Olpasiran in Healthy Japanese and Non-Japanese Participants: Results from a Phase I, Single-dose, Open-label Study

PurposeOlpasiran, an N-acetyl galactosamine–conjugated, hepatocyte-targeted, small interfering RNA, is being developed to reduce plasma lipoprotein (Lp)-(a) concentration by directly targeting the LPA gene. This study evaluated the pharmacokinetics, pharmacodynamics, and tolerability of a single SC injection of olpasiran in healthy, Japanese and non-Japanese participants. MethodsIn this Phase I, open-label, parallel-design study, Japanese participants were randomized in a 1:1:1:1 ratio to receive a single 3, 9, 75, or 225 mg dose of olpasiran. Non-Japanese participants received a single 75 mg dose of olpasiran. The primary end points were pharmacokinetic parameters, including Cmax, AUCinf, tmax, and t1/2. Tolerability and change in Lp(a) concentration were also assessed. FindingsA total of 27 enrolled participants had a mean (SD) age of 48.0 (12.5) years. Olpasiran Cmax and AUCinf were increased in an approximately dose-proportional manner in the Japanese groups. Mean (SD) Cmax values were 242 (121.0) and 144 (71.3) ng/mL, and mean (SD) AUCinf values were 3550 (592.0) and 2620 (917.0) h·ng/mL, in the Japanese and non-Japanese groups, respectively, given 75 mg of olpasiran. Median tmax ranged from 3.0 to 9.0 hours and mean (SD) t1/2 ranged from 4.0 (0.3) to 6.9 (1.6) hours across all groups. The maximal Lp(a) reduction occurred at day 57, with mean (SD) Lp(a) percentage reductions from baseline ranging from 56.0% (21.0%) to 99.0% (0.2%). A reductions in Lp(a) was observed as early as day 4. All adverse events were mild in severity, with no serious or fatal adverse events. No clinically important changes in tolerability-related laboratory analytes or vital signs were observed. ImplicationsIn this population of healthy Japanese participants, dose-proportional increases in exposure and reduced Lp(a) in a dose-dependent manner were found with single 3, 9, 75, and 225 mg doses of olpasiran. The magnitude and durability of Lp(a) reductions were similar between the Japanese and non-Japanese groups. Olpasiran was well tolerated, with no clinically important adverse events or laboratory or vital sign abnormalities.

Association of lipoprotein(a) with aortic dissection.

BackgroundLipoprotein(a) [Lp(a)] is associated with coronary atherosclerotic heart disease, aortic stenosis, stroke, and heart failure. We aimed to determine the relationship between Lp(a) and aortic dissection (AD).MethodsTwo hundred patients with AD were included in our case group. The control group consisted of 200 non‐AD people who were age‐ (±5 years) and gender‐matched to the case group. Data were collected retrospectively, including hypertension, smoking, coronary artery disease, diabetes mellitus, Lp(a), total cholesterol, triglyceride, low‐density lipoprotein cholesterol, and high‐density lipoprotein cholesterol. The association between Lp(a) and AD was studied using univariate and multivariate logistic regression analysis.ResultsPatients with AD had greater median Lp(a) concentrations than non‐AD people (152.50 vs. 81.75 mg/L). Lp(a) was associated with AD in a multivariate logistic regression analysis (odds ratio, 8.03; 95% confidence interval, 2.85–22.62), comparing those with Lp(a) quartile 4 with those with Lp(a) quartile 1. Stratified analysis showed that this relationship was observed in both men and women, as well as in older and younger individuals.ConclusionsHigh levels of Lp(a) are strongly associated with AD, independent of other cardiovascular risk factors.

Effects of Dapagliflozin in Combination with Metoprolol Sustained-Release Tablets on Prognosis and Cardiac Function in Patients with Acute Myocardial Infarction after PCI.

Objective To find the effects of dapagliflozin in combination with metoprolol sustained-release tablets on cardiac function and prognosis in acute myocardial infarction patients after PCI. Methods A total of 84 patients with myocardial infarction who experienced PCI from February 2020 to February 2022 were included and allocated into 3 groups: groups A, B, and C (n = 28/per group). Group A was given dapagliflozin combined with metoprolol sustained-release tablets, group B was given dapagliflozin, and group C was given the placebo. Left ventricular end diastolic diameter (EDD), left ventricular ejection fraction (LVEF), and end systolic diameter (ESD) were measured before and after treatment in all groups; myocardial infarction areas were matched among all three groups at 3 months posttreatment. The serum concentrations of interleukin-6 (IL-6), hypersensitive C-reactive protein (hs-CRP), superoxide dismutase (SOD), and malondialdehyde (MDA) were detected in all three groups before and after treatment. The levels of N-terminal probrain natriuretic peptide (NT-pro BNP), lipoprotein (a) (Lp(a)), ischemia-modified albumin (IMA), and secreted frizzled-related protein 5 (SFRP5) were also detected in the serum of all groups. Adverse reactions and cardiovascular adverse events were matched between all groups. Results The levels of LVEF in groups A and B were increased after treatment, while the levels of EDD and ESD were decreased. The improvement degree of LVEF and EDD levels in groups A and B was found greater compared to group C (P < 0.05). No significant difference was found in myocardial infarction area among the three groups at 3 months postoperation (P > 0.05). Serum concentrations of MDA, hs-CRP, IL-6, IMA, NT-proBNP, and Lp(a) were found to decrease in all three groups after treatment, while the levels of SOD and SFRP5 were increased. The improvement degree of serum hs-CRP, IL-6, SOD, MDA, IMA, NT-proBNP, Lp(a), and SFRP5 levels was greater in both groups A and B compared to group C. The improvement degree of serum hS-CRP, SOD, MDA, IMA, Nt-probNP, Lp(a), and SFRP5 levels was significantly greater in group A compared to group B (P < 0.05). No adverse effect was observed in all three groups (P > 0.05). Total occurrence of cardiovascular adverse effects such as stent thrombosis, heart failure, ventricular fibrillation, and death was 10.71% in group A, 25.00% in group B, and 53.75% in group C. There was statistical significance in the onset of cardiovascular adverse effects 3 months postoperation among all three groups (P < 0.05). Conclusion Dapagliflozin with metoprolol sustained-release tablets can be effective in improving the heart function, inflammatory response, oxidative stress response, and prognosis in patients after PCI.

Association between lipoprotein(a) concentrations and atherosclerotic cardiovascular disease risk in patients with familial hypercholesterolemia: An analysis from the hellas-fh

Background and Aims : Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) in the general population. However, such a role in patients with familial hypercholesterolemia (FH) is less documented. The purpose of this study was to evaluate the association between Lp(a) concentrations and ASCVD prevalence in adult patients with FH.Methods: This was a cross-sectional study from the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH). Patients were categorized into 3 tertiles according to Lp(a) levels.Results: A total of 541 adult patients (249 males) with heterozygous FH (HeFH) were included (mean age 48.5±15.0 years at registration, 40.8±15.9 years at diagnosis). Median (interquartile range) Lp(a) concentrations in the 1st, 2nd and 3rd Lp(a) tertile were 6.4 (3.0-9.7), 22.4 (16.0-29.1) and 77.0 (55.0-102.0) mg/dL, respectively. There was no difference in lipid profile across Lp(a) tertiles. The overall prevalence of CVD was 9.4% in the first, 16.1% in the second and 20.6% in the third tertile (p=0.012 among tertiles). This was also the case for premature ASCVD, with prevalence rates of 8.5%, 13.4% and 19.8%, respectively (p=0.010 among tertiles). A trend for increasing prevalence of coronary artery disease (8.3%, 12.2% and 16.1%, respectively; p=0.076 among tertiles) was also observed. No difference in the prevalence of stroke and peripheral artery disease was found across tertiles.Conclusions: Elevated Lp(a) concentrations are significantly associated with increased prevalence of ASCVD in patients with HeFH. Background and Aims : Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) in the general population. However, such a role in patients with familial hypercholesterolemia (FH) is less documented. The purpose of this study was to evaluate the association between Lp(a) concentrations and ASCVD prevalence in adult patients with FH. Methods: This was a cross-sectional study from the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH). Patients were categorized into 3 tertiles according to Lp(a) levels. Results: A total of 541 adult patients (249 males) with heterozygous FH (HeFH) were included (mean age 48.5±15.0 years at registration, 40.8±15.9 years at diagnosis). Median (interquartile range) Lp(a) concentrations in the 1st, 2nd and 3rd Lp(a) tertile were 6.4 (3.0-9.7), 22.4 (16.0-29.1) and 77.0 (55.0-102.0) mg/dL, respectively. There was no difference in lipid profile across Lp(a) tertiles. The overall prevalence of CVD was 9.4% in the first, 16.1% in the second and 20.6% in the third tertile (p=0.012 among tertiles). This was also the case for premature ASCVD, with prevalence rates of 8.5%, 13.4% and 19.8%, respectively (p=0.010 among tertiles). A trend for increasing prevalence of coronary artery disease (8.3%, 12.2% and 16.1%, respectively; p=0.076 among tertiles) was also observed. No difference in the prevalence of stroke and peripheral artery disease was found across tertiles. Conclusions: Elevated Lp(a) concentrations are significantly associated with increased prevalence of ASCVD in patients with HeFH.

Is the risk of atherosclerotic cardiovascular disease different between genotype determined or measured Lp(a) levels?

Background and Aims : Lp(a) concentration has been associated to increased risk of atherosclerotic cardiovascular disease (ASCVD). Whether ASCVD risk varies between LPA genotype or measured Lp(a) levels is still unknown.Methods: A total of 445,744 participants enrolled in the UK-Biobank with complete genetic and principal component data were included in the study. For each participant, we calculated the LPA genetic risk score by summing the number of risk-increasing alleles inherited at rs3798220 and rs10455872 variants, weighted by the effect size of each allele. The primary outcome was major coronary event (MCE), a composite of fatal or non-fatal myocardial infarction, or coronary revascularization. Using adjusted Cox proportional hazards models and Kaplan-Meier curves, we compared the cumulative lifetime risk of MCE among subjects with different LPA genotype and measured Lp(a) concentrations.Results: Participants with one copy of either rs10455872 or rs3798220 had a hazard ratio (HR) for MCE of 1.47 (95%CI: 1.42-1.51) compared with wild-type subjects (median Lp(a): 146.3 nmol/L and 13.6 nmol/L, respectively). Stratifying the population according to measured Lp(a) concentrations comparable to those observed for the genetic risk score, we found similar rate of incident MCE for the same Lp(a) change (HR 1.47, 95%CI: 1.41-1.53). Even among subjects with the same LPA genotype, increasing quintiles of Lp(a) concentration were associated with a step-wise increase in MCE risk.Conclusions: Our results demonstrated that LPA genetic risk score and measured Lp(a) concentrations provide comparable risk prediction for incident MCE. In terms of cardiovascular risk prediction, it is reasonable to rely on clinically measured Lp(a) levels, regardless of genotype. Background and Aims : Lp(a) concentration has been associated to increased risk of atherosclerotic cardiovascular disease (ASCVD). Whether ASCVD risk varies between LPA genotype or measured Lp(a) levels is still unknown. Methods: A total of 445,744 participants enrolled in the UK-Biobank with complete genetic and principal component data were included in the study. For each participant, we calculated the LPA genetic risk score by summing the number of risk-increasing alleles inherited at rs3798220 and rs10455872 variants, weighted by the effect size of each allele. The primary outcome was major coronary event (MCE), a composite of fatal or non-fatal myocardial infarction, or coronary revascularization. Using adjusted Cox proportional hazards models and Kaplan-Meier curves, we compared the cumulative lifetime risk of MCE among subjects with different LPA genotype and measured Lp(a) concentrations. Results: Participants with one copy of either rs10455872 or rs3798220 had a hazard ratio (HR) for MCE of 1.47 (95%CI: 1.42-1.51) compared with wild-type subjects (median Lp(a): 146.3 nmol/L and 13.6 nmol/L, respectively). Stratifying the population according to measured Lp(a) concentrations comparable to those observed for the genetic risk score, we found similar rate of incident MCE for the same Lp(a) change (HR 1.47, 95%CI: 1.41-1.53). Even among subjects with the same LPA genotype, increasing quintiles of Lp(a) concentration were associated with a step-wise increase in MCE risk. Conclusions: Our results demonstrated that LPA genetic risk score and measured Lp(a) concentrations provide comparable risk prediction for incident MCE. In terms of cardiovascular risk prediction, it is reasonable to rely on clinically measured Lp(a) levels, regardless of genotype.

Optimization and validation of lipoprotein(a) KIV2 isoform measurement in patients with familial hypercholesterolemia

Background and Aims : Positive correlation is shown between concentration of Lp(a) and severity of coronary artery disease (CAD). Elevated Lp(a) levels are associated with restenosis after percutaneous coronary intervention (PCI). Copenhagen City Heart Study (CCHS) found that extreme Lp(a) levels > 95th percentile predict 3- to 4-fold increase in risk of myocardial infarction. European Atherosclerosis Society (EAS) Consensus Panel recommends screening patients for elevated Lp(a). We evaluated PCR efficiency/ coefficient of variation of Lp(a) KIV-2 repeat genotyping assay, and correlated repeat size in patients with familial hypercholesterolemia with confirmed mutation and mutation negative patients.

The frequencies of infgamma-producing t-helpers 17 and Lp(a) concentration in blood in patients with atherosclerosis

Background and Aims : Chronic inflammation accompanied by the innate and adaptive immune response as well as lipid disorders are key players in atherogenesis. We analyzed the content of minor T-cell populations with pro- and ant-inflammatory activity, the concentration of lipoprotein(a) [Lp(a)] and markers of neutrophil activation in patients with atherosclerosis.

Triglyceride metabolism modifies lipoprotein(a) plasma concentration

Background and Aims : Lipoprotein(a) (Lp(a)) is a significant cardiovascular risk factor. This study aimed to analyze the relationship between triglycerides (TG) and Lp(a) concentrations, cross-sectionally and longitudinally, and the influence of the number and composition of TG-rich lipoproteins, and the APOE genotype.

The effect of the LPA variant P.THR3888PRO on lipoprotein(a) and coronary artery disease is modified by the LPA KIV-2 splice site variant 4925g>A

Background and Aims : Lipoprotein(a) [Lp(a)] plasma concentrations are mainly regulated by the LPA gene. Besides the KIV-2 repeat (a complex copy number variation), multiple SNPs pronouncedly modify Lp(a) levels (e.g. the recently described KIV-2 variant 4925G>A). However, little is known about non-linear and/or epistatic mechanisms and SNP interactions. Thus, we investigated the impact of the interaction between the largely investigated LPA variant p.Thr3888Pro (rs41272110) and the KIV-2 variant 4925G>A on Lp(a) concentration and CAD risk.

Differential associations of lipoprotein(a) level with cerebral large artery and small vessel diseases

Background and purposeCerebral large artery and small vessel diseases are related to different pathogenetic mechanisms and have different risk factor profile. Lipoprotein(a) (Lp(a)) was shown to promote atherosclerosis but data...

Long-term tracking and population characteristics of lipoprotein (a) in the Cardiovascular Risk in Young Finns Study

Background and aimsLipoprotein (a) (Lp(a)) is a causal risk factor for cardiovascular diseases and its levels are under strict genetic control. Therefore, it is hypothesized that the concentration of Lp(a) remains stable throughout life. Finns have lower Lp(a) levels than central Europeans, but it is unknown whether there are differences within Finland, especially between the eastern and western parts of the country with known genetic duality and persistent differences in cardiovascular disease rates. We have examined the long-term stability of Lp(a) levels over 25 years in the Cardiovascular Risk in Young Finns Study (YFS), and the characteristics of individuals with different Lp(a) levels, including their geographical origin within Finland. MethodsIn YFS, the first large baseline examination was conducted in 1980 (baseline age, 3–18 years). Several follow-ups during the past 40 years have been conducted to investigate the determinants of cardiometabolic health. Lp(a) levels have been measured in study years 1986 (N = 2464, ages 9–24 years), 2001 (N = 2281, ages 24–39 years), 2007 (N = 2204, ages 35–45 years) and 2011 (N = 2044, ages 39–49 years). Tracking of Lp(a) was estimated by calculating Spearman's rank order correlations between the study years, and by cross-tabulating how many individuals diagnosed with either elevated or non-elevated Lp(a) levels in 1986, 2001 and 2007 remained in the same category in the latest follow-up in 2011. ResultsSpearman's correlation coefficients varied between r = 0.84–0.96. Most individuals (87–94%) who had a high Lp(a) level (>30 mg/dl) in any of the previous study years had a high level also in 2011. On average, the median Lp(a) levels were consistently ∼20% higher in the individuals originating from eastern Finland compared to those from western Finland, but there were no differences in the distribution of known genetic determinants between eastern and western Finns that would have explained the observed difference. ConclusionsThese data confirm that Lp(a) levels remain very stable over the life-course. In line with the genetic duality between eastern and western parts of Finland, we observed about 20% higher Lp(a) levels in individuals originating from eastern Finland compared to those originating from western Finland.

Triglyceride Metabolism Modifies Lipoprotein(a) Plasma Concentration.

Lipoprotein(a) (Lp(a)) is a significant cardiovascular risk factor. Knowing the mechanisms that regulate its concentration can facilitate the development of Lp(a)-lowering drugs. This study analyzes the relationship between triglycerides (TGs) and Lp(a) concentrations, cross-sectionally and longitudinally, and the influence of the number and composition of TG-rich lipoproteins, and the APOE genotype. Data from Aragon Workers Health Study (AWHS) (n = 5467), National Health and Nutrition Examination Survey III phase 2 (n = 3860), and Hospital Universitario Miguel Servet (HUMS) (n = 2079) were used for cross-sectional TG and Lp(a) relationship. Lp(a) intrasubject variation was studied in AWHS participants and HUMS patients with repeated measurements. TG-rich lipoproteins were quantified by nuclear magnetic resonance in a subsample from AWHS. Apolipoproteins B and E were quantified by Luminex in very low-density lipoprotein (VLDL) isolated by ultracentrifugation, from HUMS samples. APOE genotyping was carried in AWHS and HUMS participants. Regression models adjusted for age and sex were used to study the association. The 3 studies showed an inverse relationship between TG and Lp(a). Increased VLDL number, size, and TG content were associated with significantly lower Lp(a). There was an inverse association between the apoE concentration in VLDL and Lp(a). No significant association was observed for apolipoprotein (apo)B. Subjects carrying the apoE2/E2 genotype had significantly lower levels of Lp(a). Our results show an inverse relationship Lp(a)-TG. Subjects with larger VLDL size have lower Lp(a), and lower values of Lp(a) were present in patients with apoE-rich VLDL and apoE2/E2 subjects. Our results suggest that bigger VLDLs and VLDLs enriched in apoE are inversely involved in Lp(a) plasma concentration.

Lipoprotein Subfractions as Markers for Predicting the Presence and Severity of Coronary Artery Disease in Patients Undergoing Coronary Angiography.

Patients with coronary artery disease (CAD) often have normal blood cholesterol profiles that make it difficult to identify those at risk. The role of lipoprotein subfractions in the development of CAD has attracted increasing attention, and can further stratify risks. We enrolled 1578 patients undergoing coronary angiography and not taking any lipid-lowering drugs; 1033 of them were diagnosed with CAD. The severity of CAD was assessed using Gensini score (GS) and divided into 3 groups. Multivariate regression analysis showed that low-density lipoprotein particle 6 (LDL-P6) and lipoprotein (a) (Lp(a)) were independent risk factors for CAD, apart for the traditional risk factors. In receiver-operating characteristic (ROC) analysis for predicting the presence of CAD, the area under the ROC curve of traditional risk factors combined with Lp(a) and LDL-P6 for predicting CAD was .723, which was better than for traditional risk factors (P = .023). The plasma LDL-P6 and Lp(a) concentrations in the highest tertile GS group were significantly higher than that in the lowest GS group (P < .001). Stepwise linear regression analysis demonstrated positive correlations between Lp(a), LDL-P6 and GS (P = .007 and P < .001). LDL-P6 and Lp(a) are useful markers for predicting the presence and severity of CAD.

Lipoprotein(a): Insights for the Practicing Clinician.

Following the discovery of the Lipoprotein(a) (Lp(a)) molecule by Kare Berg in 1963, many physiological and pathological properties of this particle remain to be fully understood. Multiple population-based studies have demonstrated a correlation between elevated Lp(a) levels and the incidence of cardiovascular disease. Data extrapolated from the Copenhagen City Heart and ASTRONOMER studies also demonstrated the link between Lp(a) levels and the incidence and rate of progression of calcific aortic stenosis. Interest in Lp(a) has increased in recent years, partly due to new emerging therapies that can specifically reduce serum Lp(a) concentrations. Given the strong correlation between Lp(a) and CV disease from epidemiological studies, several international guidelines have also been updated to advocate Lp(a) testing in specific population groups. This review aims to highlight the importance of the role of Lp(a) in cardiovascular disease and discusses the potential of novel therapies in patients with elevated Lp(a) levels.

Lipoprotein apheresis in patients with familial hypercholesterolemia: a single center research

Objective: We evaluated the safety and efficacy of lipoprotein apheresis (LA) in patients with familial hypercholesterolemia (FH) who can't reach low-density lipoprotein cholesterol(LDL-C) target goals with the maximal tolerated dose of lipid-lowering agents. Methods: This was a retrospective cross-sectional study. Between February 2015 and November 2019, patients with FH who were admitted in Fuwai hospital and treated with LA were consecutively enrolled. Based on intensive lipid-lowering agents, these patients received LA by double filtration plasma pheresis (DFPP) method. The changes of lipid levels such as LDL-C and lipoprotein(a)[Lp(a)] were compared before and after LA treatment, and the changes of immunoglobulin (Ig) concentration and LA-related adverse effects were also discussed. Results: A total of 115 patients with FH were enrolled in this study, of which 8 cases were homozygous FH and 107 cases were heterozygous FH. The age was (43.9±12.2) years and there were 75 (65.2%) males, and 108 (93.8%) with coronary artery disease. For pre-and immediately after LA treatment, the LDL-C was (5.20±2.94) mmol/L vs. (1.83±1.08) mmol/L, Lp(a) concentration was 428.70(177.00, 829.50)mg/L vs. 148.90(75.90, 317.00) mg/L (P<0.001), with a decrease of 64.2% and 59.8% respectively. The levels of IgG and IgA measured 1 day after LA treatment were both in the normal range and IgM concentration was below the reference value, the reductions of which were 15.1%, 25.0% and 58.7% respectively (P<0.001). Six patients had mild symptoms of nausea, hypotension dyspnea and palpitation, the symptoms were relieved by symptomatic treatment. Conclusion: For patients with FH who do not achieve LDL-C target goal with the maximal tolerated lipid-lowering agents, especially those with elevated Lp(a) levels, LA, which can significantly further reduce LDL-C and Lp(a) levels, is an effective and safe option.

The Curious Case of Synergy between Lipoprotein (a), Coronary Calcification, and Cardiovascular Disease Risk.

Despite recent advances in cardiovascular interventions and preventive therapies, there remains a substantial residual risk of atherosclerotic cardiovascular disease (ASCVD), even among patients on maximal guideline-directed medical therapy. Growing epidemiological and genetic evidence supports the causal role that lipoprotein(a) [Lp(a)], an apolipoprotein-B–containing lipoprotein, plays in increasing the risk of ASCVD morbidity and mortality, and an elevated Lp(a) (≥50 mg/dL or ≥125 nmol/L) is considered a risk enhancer in recent national guidelines (1). Multiple proinflammatory, proatherogenic, procalcific, and cellular signaling mechanisms have been described that could mediate the association of Lp(a) with ASCVD clinical events, in particular due to the oxidized phospholipid content of Lp(a) (2). An intriguing finding has been that elevated Lp(a) concentrations do not associate with prevalent coronary artery calcification (CAC) despite being associated with more rapid progression of CAC and atherosclerotic plaque (3). But while prior studies have shown no association between prevalent Lp(a) and CAC, the joint association of Lp(a) and CAC with the risk of future ASCVD events is not well understood (4). CAC, measured on computed tomography, is an established risk enhancer incorporated into recent guidelines to favor initiation or intensification of statin therapy in patients with uncertain ASCVD risk. On the other hand, the absence of CAC has been used to favor withholding or delaying statin use in certain patients (1).

Elevated lipoprotein(a) as a predictor for coronary events in older men

Elevated circulating lipoprotein (a) [Lp(a)] is associated with an increased risk of first and recurrent cardiovascular events; however, the effect of baseline Lp(a) levels on long-term outcomes in an elderly population is not well understood. The current single-center prospective study evaluated the association of Lp(a) levels with incident acute coronary syndrome to identify populations at risk of future events. Lp(a) concentration was assessed in 755 individuals (mean age of 71.9 years) within the community and followed for up to 8 years (median time to event, 4.5 years; interquartile range, 2.5–6.5 years). Participants with clinically relevant high levels of Lp(a) (>50 mg/dl) had an increased absolute incidence rate of ASC of 2.00 (95% CI, 1.0041) over 8 years (P = 0.04). Moreover, Kaplan-Meier cumulative event analyses demonstrated the risk of ASC increased when compared with patients with low (<30 mg/dl) and elevated (30–50 mg/dl) levels of Lp(a) over 8 years (Gray’s test; P = 0.16). Within analyses adjusted for age and BMI, the hazard ratio was 2.04 (95% CI, 1.0–4.2; P = 0.05) in the high versus low Lp(a) groups. Overall, this study adds support for recent guidelines recommending a one-time measurement of Lp(a) levels in cardiovascular risk assessment to identify subpopulations at risk and underscores the potential utility of this marker even among older individuals at a time when potent Lp(a)-lowering agents are undergoing evaluation for clinical use.

Lipoprotein(a): An Independent Risk factor of Cardiovascular Disease

Background: Cardiovascular disease is currently one of the most common causes of morbidity and mortality in developed and developing countries. Many traditional risk factors such as age, gender, smoking, diabetes mellitus, dyslipidemia and hypertension play an important role in the development of vascular disorders. Lipoprotein (a) or Lp (a), an intriguing lipoprotein particle is also considered to be an important risk factor for the development of cardiovascular disease. Lp(a) is a LDL-like molecule consisting of an apolipoprotein B-100 (apo B-100) particle attached by a disulphide bridge to a unique protein, apolipoprotein(a)/ apo(a) which distinguishes it from LDL. Many epidemiological studies have reported the positive associations of Lp(a) concentration with atherosclerosis, coronary artery disease and stroke.&#x0D; Central Medical College Journal Vol 5 No 1 Jan 2021 PP 51-58

Lipoprotéine(a) et risque cardiovasculaire

AbstractDiscovered 60 years ago, lipoprotein (a) was very quickly recognized as an independent cardiovascular risk factor when its genetically determined concentration was high. Lp(a) is a lipoprotein containing apolipoprotein B100 like LDL but distinguished by the presence of an apolipoprotein (a) molecule. This apo(a) exhibits a very great structural heterogeneity as a function of the number of copies of the “kringle IV2” motif, making it possible to distinguish between small isoforms and large isoforms. The plasma concentration of Lp(a) is inversely proportional to the size of the apo(a) present in the Lp(a). The atherogenic properties of Lp(a) are linked to the LDL fraction, its thrombogenic properties are due to the anti- fibrinolytic action of apo(a) due to its partial homology with plasminogen. More recently a role in vascular calcification has also been demonstrated. During the 2000s, interest in Lp(a) declined considerably. Lp(a) is now back in the spotlight because its dosage makes it possible to improve the identification and management of subjects at high cardiovascular risk and because new therapies to reduce the synthesis of apo(a) look promising.

The relationship between the level of Lр(а) and the prevalence of atherosclerosis among young patients

Hyperlipoproteinemia (a) is an independent and cause risk factor for atherosclerotic cardiovascular diseases (ASCVD). The correlation between lipoprotein (a) Lp(a) and inflammation in the vessel wall was actively studied during the past few years. C-reactive protein (CRP) plays an important role in ASCVD. To analyze the relationship between hyperlipoproteinemia (a), inflammatory markers, and the early development of stenosing atherosclerosis (AS) in several vascular pools. 76 patients, 55 men aged 18 to 55 years and 21women 18 to 60 years, with the results of instrumental examination of coronary, carotid and lower extremities vascular pools were enrolled. Three groups: with stenosing (50%) AS of only one (group 1, n=29); two or three (group 2, n=21) vascular pools. 26 patients without coronary heart disease and AS were included in the control group. All patients in groups 1 and 2 and 65% of those in the control group took statins. The concentrations of Lp(a), CRP, lipids and blood count were determined. The patients of the three groups did not differ in age. In the groups with AS (79% in group 1 and 85% in group 2), there were more men (relative to 54% in the control group). Diabetes mellitus was more common only in patients with multifocal AS. The absolute number of blood monocytes and leukocytes, the neutrophil-lymphocyte ratio, as well as Lp(a) level were higher in patients of groups 1 and 2 relative to the control. The maximum Lp(a) level (median [25%; 75%]) was observed in patients with lesions of two or more vascular pools vs the control group (49 [4; 96] mg/dL, vs 10 [4; 21] mg/dL, p=0.02). The CRP level was significant elevated in patients from group 2 7.2 [4.0; 9.7] mg/L, relative to group 1 2.5 [1.0; 4.7] mg/L, and the control group 2.9 [1.2; 4.9] mg/L, p0.05. The Lp(a) and CRP concentration, or the presence of diabetes mellitus in patients, regardless of other risk factors, were associated with severe stenosing AS in young and middle age. An elevated concentration of Lp(a) (30 mg/dL) determines the presence of both isolated and multifocal stenosing AS in the examined patients. A simultaneous increase in the concentration of both Lp(a) and CRP, as well as the presence of diabetes mellitus, are associated with the premature development of stenosing atherosclerotic lesions in several vascular regions at once. Measurement of these predictors in young and middle-aged patients makes it possible to use them as biochemical markers to assess the likelihood of multifocal lesions of the vascular pool.